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We studied the effect of melatonin (10 mg/kg intraperitoneally) on behavioral indexes reflecting changes in nociceptive sensitivity of rats in response to thermal stimulation in the hot plate test. Administration of melatonin to animals suppressed the perceptual component of nociception, which was manifested in an increase in the perception threshold of noxious thermal stimulus. In the follow-up period, exogenous melatonin contributed to a decrease in the latency of avoidance reactions and enhanced the behavior of escaping the thermal nociceptive stimulation. Our results suggest that the involvement of melatonin in goal-directed behavior of mammals during nociceptive treatment is related to an increase in orientation and exploratory activity, facilitation of memory storage, and improvement of memory retrieval for environmental signals, action program, and reinforcing effect of avoiding the painful stimulus.

The effect of the epiphyseal hormone melatonin on the activity of antioxidant enzymes, glutathione peroxidase (GPx), glutathione reductase (GR), and Cu/Zn-superoxide dismutase (Cu/Zn-SOD) was studied in peripheral blood erythrocytes of behaviorally passive and active Wistar rats. Acute emotional stress was modeled by immobilization of animals for1 h with simultaneous electrocutaneous stimulation. Basal activity of antioxidant glutathione enzymes in erythrocytes of behaviorally passive rats was higher than that in active animals. Administration of melatonin (2 mg/kg, intraperitoneally) was accompanied by a decrease in the activity of GPx and GR in erythrocytes from non-stressed passive animals. After experimental stress, passive rats demonstrated a significant increase in the activity of Cu/Zn-SOD and GPx in peripheral blood erythrocytes. The absence of stress-induced changes in functional activity of antioxidant defense enzymes in the blood of behaviorally active animals suggests a relatively constant oxidative status of tissues in these animals under stress conditions. Melatonin administration had little effect on stress-induced changes in functional activity of the erythrocyte antioxidant system in passive rats. Active specimens pretreated with melatonin before stress exposure were characterized by activation of study antioxidant enzymes. Quantitative parameters of the erythrocyte antioxidant defense enzymes did not differ in behaviorally active and passive rats subjected to experimental stress after melatonin injection. Thus, exogenous melatonin abolishes differences in the activity of study antioxidant enzymes in erythrocytes of animals with different behavioral parameters under basal conditions and after experimental stress. In passive rats melatonin mainly reduced the initial tension of oxidative processes. By contrast, administration of this hormone to active specimens is followed by an increase in functional activity of the antioxidant enzyme system under conditions of acute stress.

This work was designed to study the effect of melatonin on lipid peroxidation in the peripheral blood of behaviorally passive and active Wistar rats. Immobilization of rats with simultaneous electrocutaneous stimulation (1 h) served as a model of acute stress. After intraperitoneal injection of melatonin (2 mg/kg) the intensity of lipid peroxidation in the blood plasma remained practically unchanged in passive specimens, but increased in active animals. Stress exposure was followed by specific variations in free radical processes in the blood (passive rats, inhibition; active specimens, no changes). Administration of melatonin contributed to a decrease in the intensity of lipid peroxidation in the blood of stressed rats (as compared to control specimens receiving this neurohormone). Therefore, the effect of melatonin on free radical processes depends on the initial behavioral characteristics and physiological state of animals. These data illustrate the importance of an individual approach to studying the systemic mechanisms for organization of functions in mammals. Key words: melatonin, emotional stress, lipid peroxidation, blood plasma, rats with various behavioral characteristics.

The effects of melatonin (epiphyseal neurohormone) on the serum cytokine profiles of rats with different behavioral characteristics were studied after acute emotional stress. One-hour immobilization of animals with simultaneous electrocutaneous stimulation of subthreshold intensity served as the stress model. Acute stress exposure of animals with active behavior led to reduction of the peripheral blood concentrations of pro-inflammatory (IL-1α, IL-1β, IL-2, IFN-γ, granulomonocytic CSF) and anti-inflammatory (IL-4, IL-10) cytokines. Passive rats exposed to emotional stress developed a pronounced increase of pro-inflammatory IL-1β concentration. Reduction of pro-inflammatory cytokine levels in active rats exposed to stress was less pronounced after intraperitoneal preinjection of melatonin (2 mg/kg). In passive animals, exogenous melatonin inverted the poststress changes in the serum levels of pro-inflammatory IL-2 cytokine and of anti-inflammatory IL-4 and IL-10 cytokines. The modulatory effect of melatonin on the cytokine profiles of rats with different behavioral parameters seemed to contribute to adaptation of animals to emotional stress exposure.

This report describes studies of the effects of shifts in the daily light/dark rhythm and administration of different doses of melatonin on the behavior of rats with different activity in the open field test. Experiments were performed on 172 Wistar rats kept in a natural or an inverted light/dark regime. Groups of rats received 1 ml of physiological saline or melatonin (1 or 2 mg/kg, i.p.) or were not injected. Inversion of the light/dark regime led to a shift in the rhythm of movement activity and eliminated differences between measures of daytime and night-time activity in control rats not given injections. The effect of melatonin on the movement activity of rats in conditions of natural and inverted light regimes depended on the dose given, the time of administration, and the initial characteristics of the animals' behavior. The data obtained here show that use of melatonin to correct impairments induced by the shift in the light/dark cycle should take consideration of the individual behavioral characteristics of the subjects.

We studied the role of the hypothalamic suprachiasmatic nucleus in realization of the effect of melatonin on stress marker organs in rats under normal conditions and during acute stress. Stress induced involution of the thymus in active rats and adrenal gland hypertrophy in active and passive animals. Electrocoagulation of the suprachiasmatic nucleus induced a more pronounced decrease in the weight of the thymus and greater increase in the weight of the adrenal glands. Melatonin administration after electrocoagulation of the suprachiasmatic nucleus had no effect on the relative weight of the thymus, adrenal glands, and spleen in control and stressed animals. The influence of melatonin on the thymus, adrenal glands, and spleen is partly mediated by this structure of the brain.

We studied the effects of acute stress and exogenous melatonin on stress marker organs in rats. Administration of melatonin under normal conditions increased the relative weights of the thymus (active rats) and adrenal glands (active and passive rats). The relative weight of the spleen also tended to increase after melatonin treatment. Stress led to involution of the thymus and hypertrophy of the adrenal glands in active and especially in passive animals receiving physiological saline. Melatonin partially or completely prevented involution of the thymus under stress conditions. Stress had no effect on the relative weight of the adrenal glands in melatonin-treated rats. The relative weight of the spleen in active rats receiving melatonin in doses of 0.5 and 1 mg/kg decreased after stress exposure. Our results suggest that melatonin modulates the hemodynamics and function of stress marker organs.

We studied the effect of shift in the natural light/dark regimen (desynchronosis) and treatment with melatonin on behavioral characteristics of rats with different activity in the open-field test. Experiments were performed on 172 Wistar rats kept under conditions of the natural or shifted light/dark regimen. Some animals were intraperitoneally treated with 1 ml physiological saline or melatonin in doses of 1 and 2 mg/kg, while others did not receive the injections. Desynchronosis altered the normal rhythm of locomotor activity and abolished the differences between daytime and nighttime activity rats not receiving the injections. The influence of melatonin on locomotor activity of rats maintained under normal or shifted light/dark conditions depended on its dose, time of treatment, and initial behavioral characteristics of animals. Our results indicate that the use of melatonin for treatment of disturbances produced by a shift in the light/dark conditions should be performed taking into account individual behavioral characteristics of the organism.

Effects of phase shifts in circadian rhythms and of melatonin administration on rectal temperature in rats with different activity were studied in the open-field test on 176 Wistar rats kept under conditions of natural or shifted light-darkness period. Under normal light-darkness conditions, the amplitude of diurnal variation in rectal temperature was higher in active rats as compared with passive ones. A shift in the light-darkness conditions inverted the circadian rhythm of rectal temperature and augmented the difference between daytime and night time temperatures in passive and, particularly, in active rats. Melatonin effect depended on dose and time of administration. 1 mg/kg Melatonin enhanced the amplitude of diurnal rhythms of energy metabolism in behaviourally active rats. These changes seem to contribute to adaptive reconstruction in the organism during desynchronosis.

We studied the effects of acute stress and exogenous melatonin in various doses on the intensity of lipid peroxidation in emotiogenic structures of the brain and liver of rats with different activity in the open field. Stress had no effect on the content of malonic dialdehyde in the hypothalamus, sensorimotor cortex, and liver of active and passive rats receiving physiological saline. The influence of melatonin on malonic dialdehyde content depended on the dose of this substance. The amount of malonic dialdehyde in brain structures (active and passive rats) and liver (active rats) increased after administration of exogenous melatonin in doses of 0.5 and 2 mg/kg, but decreased after treatment with the hormone in a dose of 1 mg/kg. Melatonin in various doses decreased malonic dialdehyde content in the liver of passive rats. The effects of melatonin are partly related to modulation of lipid peroxidation in central and peripheral tissues of the organism.

Microiontophoretic application of melatonin to the perineuronal space of nerve cells in the lateral hypothalamus of WAG and Fischer-344 rats led to decreases in the frequency and regularization of the spike activity of neurons, and also blocked activation of neurons and changing the patterns of adrenaline-induced spike activity. The effects of melatonin were more marked in WAG rats, which demonstrated the more active behavior in the open field test and were predicted to be more resistant to emotional stress, than in passive Fischer-344 rats, with predisposition to emotional stress. These results suggest that the mechanism of the stress-protective action of melatonin involves suppression of the spike activity of neurons in emotiogenic brain structures and changes in their sensitivity to noradrenaline.

We studied the effect of acute stress on serum melatonin concentration, content of major components in the connective tissue (uronic acids, hexosamines, and hydroxyproline), and beta-galactosidase activity in the skin of rats with different activity in the open-field test receiving intraperitoneal injections of physiological saline or melatonin. Acute stress intensified catabolism of carbohydrate components and affected characteristics of the main skin biopolymers. The content of uronic acids in connective tissue carbohydrates decreased. Collagen structures of the skin underwent less pronounced changes. The observed changes were similar in behaviorally active and passive animals. Administration of melatonin increased the contents of uronic acids and hexosamines in the skin. Pretreatment with melatonin prevented the decrease in the content of glycosaminoglycans in rat skin during acute stress.

We studied the effect of a phase shift in circadian rhythms (desynchronosis) on the development of erosive and ulcerative lesions in the gastric mucosa in male Wistar rats with different behavioral activity in the open-field test. The animals kept under conditions of natural or shifted light-dark cycle were untreated or intraperitoneally received physiological saline (1 ml) and melatonin (1 or 2 mg/kg). Desynchronosis induced gastric ulcers in active rats not receiving injections or intraperitoneally injected with physiological saline. No gastric ulcers were found in passive animals kept under shifted light-dark cycle. Melatonin induced gastric ulcers in passive animals kept under natural light-dark cycle. Gastric ulcers were not found in active rats subjected to desynchronosis and receiving melatonin. Our results indicate that treatment with melatonin for the correction of changes induced by shifts in the light-dark cycle should be performed taking into account individual behavioral characteristics.

Microionophoretic administration of melatonin into the perineuronal space of lateral hypothalamic neurons in WAG and Fischer-344 rats decreased the firing rate and regularized activity of the cells. Moreover, the effects of melatonin completely blocked the activation of neurons and changes in their pulse activity produced by norepinephrine. The effects of melatonin on neuronal activity in behaviorally active stress-resistant WAG rats were more pronounced than in behaviorally passive stress-predisposed Fischer-344 rats. These data suggest that stress-protective activity of melatonin is associated with inhibition of the pulse activity of neurons in emotiogenic structures of the brain and changes in neuronal sensitivity to norepinephrine.

The study was made on Wistar rats. A shift in endogenous biological rhythms was simulated by that in the light phase by 12 hours and evaluated by the shift in the rhythm of rectal temperature. Experiments revealed that desynchronization potentiated ulcerative processes in the rat stomach. The study demonstrated the protective effect of intraperitoneally injected melatonin to prevent the formation of ulcerative defects in the rat stomach during artificially simulated desynchronization.

Blood serum melatonin concentrations were measured in male Wistar rats exposed to acute water-immersion emotional stress (ES) during intraperitoneal injections of physiological saline or different doses of melatonin. ES increased blood melatonin levels in rats receiving physiological saline 1 hour before or just after ES. When physiological saline was administered just ES, blood melatonin concentrations remained unchanged. The blood levels of melatonin both in control and stressed animals injected with exogenous melatonin were higher than those in rats given physiological saline alone. Immersion ES decreased blood melatonin concentrations in rats receiving different exogenous melatonin doses just before ES. However, in rats given melatonin, 1.0 mg/kg, after ES, its blood levels after ES was higher than those in the animals unexposed to stress. The findings suggest that it is just exogenous rather than endogenous melatonin that is consumed in rats injected with its different doses just prior to immersion ES.